Page:EB1911 - Volume 27.djvu/819

Rh methyl derivatives of isocyanic acid, and nitramide, N H2NO2. Amidourea, or semicarbazide, NH2-CO-NH-NH2, is best prepared from hydrazine sulphate and potassium cyanate (]. Thiele and O. Stange, Ber., 1894, 27, p. 31). It may also be obtained by reducing nitrourea in acid solution with zinc dust. It crystallizes in prisms, which melt at 96° C., and are easily soluble in water. It reduces Fehling's solution in the cold. It reacts with carbonyl compounds, giving semi-carbazones, and in consequence is frequently used for characterizing such substances. Hydroxy-urea, NH2~Cg-NH-OH, is produced from hydroxylamine and cyanic acid (W. F. Dresler and R. Stein, Ann., 1869, 150, p. 242), or from ammonium hypochlorite and potassium cyanate (A. Hantzsch, Ann., 1898, 299, p. 99). It crystallizes in needles, which melt at 128»130° C., an is decomposed on long heating. It is readily soluble in water and reduces warm silver solutions. Hyponitrous acid is formed by passing nitrous fumes into its methyl alcohol solution. Alkyl ureas are formed by the action of prima or secondary amines on isocyanic acid or its esters: COEH-1-N H2R= R-NHCONHQ; CONR+NHR2=NR2-CO-NHR; by the action of carbonyl chloride on amines: COCl2+2NHR2=CO(NR2)2+2HCl; and in the hydrolysis of many ureides. The tetra-alkyl derivatives are liquids, the remainder being solids. Hydrolysis by alkalis decomposes them into carbon dioxide, amines and ammonia. The symmetrically substituted ureas are generally tasteless, while the asymmetrical derivatives are sweet. For example, aa.-dimethyl urea is sweet, aB-dimethyl urea is tasteless; p-phenetol carbamide or dulcin, NH2-CO-NH-CGH4-OC2H5, is sweet, while the di-p-phenetol carbamide, CO(NH-C5H4~OC2H5)¢, is tasteless.

The derivatives of urea containing acid radicles are known as ureides. Those derived from mono basic acids, obta.ined by the action of acid chlorides or anhydrides on urea, decompose on heating and do not form salts. Those containing more than one acyl group are formed by the action of carbonyl chloride on acid amides: COCl2+2CH3CONH2 = CO(NHCOCHa)2-l-2HCl.

Acetyl urea, NH2-CO-NH-COCH3, formed by the action of acetic an hydride on urea, crystallizes in needles which melt at 212° C. and, on heating, strongly decomposes into acetamide and cyanuric acid. Methyl acetyl urea, CHQNH-CO-NHCOCH3, is formed by the action of potash on a mixture of bromine (1 mol.) and acetamide (2 mols.) (A. W. v. Hofmann, Bef., 1881, 14, p. 2725), or of methyl amine on acetylurethane (Cr. Young, Jour. Chem. Soc., 1898, 73, p. 363). When heated with water it is decomposed into carbon dioxi e, ammonia, methyl amine and acetic acid. Bromural or a-bromisovaleryl urea, NH2-CO-NH-CO~CHBr-Cl-I(CH;,)2, has been introduced as an hypnotic; its action is mild, and interfered with by the presence of pain, cough or delirium.

The ureides of oxy-acids and dibasic acids form closed chain compounds (see ALLANTOIN; ALLOXAN; HYDANTOIN; PURIN). Parabamk: acid (oxalyl urea), CO[NH-CO]2, is formed by oxidizing uric acid; or by condensing oxalic acid and urea in the presence of phosphorus oxychloride. It crystallizes in needles and is readily iiydrolysed by alkalis. It behaves as a mono basic acid and forms unstable salts. When heated with urea, it forms oxalyl diureide, H¢N-CO-CO~NH~CO-NH-CO-Nl-12. Dimelhylparabanic acid (cholesterophane), CO[NCHa-CO]¢, is formed by oxidizing caffeine or by methylating parabanic acid. It crystallizes in plates, which melt at 145' 5° C., and is soluble in cold water. Hydrochloric acid at 200° C. decomposes into oxalic acid, carbon dioxide and methyl amine, whilst an alcoholic solution of a caustic alkali gives dimethyl urea and oxalic acid. Barlrituric acid (malonyl urea), CH2 CO-NH]CO-21-l¢O, formed by condensing malonic acid with urea E. Grimaux, Bull. Soc. Chem., 1879, 31, 146), crystallizes in prisms, which decompose on heating. It yields a nitroso derivative, is nitrated by nitric acid to dilituric acid and brominated by bromine. It is a dibasic acid. Veronal (q.v.) is diethyl malonyl urea. For isobar bit uric acid see T. B. Johnson and E. V. McCollum, Jour. Biol. Chem., 1906, 1, p. 437. Tartronyl urea (dialuric acid), CO[NH-CO]CH-OH, formed by the reduction of alloxan (J. v. Liebig and F. W6hler, Ann., 1838, 26, p. 276), or of alloxantin (A. Baeyer, Ann., 1863, 127, p. 12), crystallizes in needles or prisms and possesses a very acid reaction. It becomes red on exposure, and in the moist condition absorbs oxygen from the air, giving alloxantin. Allophanic acid, NH2-CO-NH-CO2H, is not known in the free state, as when liberated from its salts, it is decomposed into urea and carbon dioxide. Its esters are formed by passing the vapours of cyanic acid into alcohols (W. Traube, Bef., 1889, 22, p. 1572): CONH -$NHz'  NHQCO- NH~CO2R;

by the action of chlorcarbonic esters on urea (H. Schiff, Ann? 1896, 291, p. 367); and by the action of urethane's on urea chloride (L. Gattermann, Ber., 1888, 21, p. 293 R). They are readily decomposed by alkalis, yielding cyanuric acid and ammonia. Biuret (allophanamide), NH2-CO~NH-CO-NH2, is formed by heating urea; by the action of ammonia on allophanic ester; and by heatin urea to 140° C. and passing chlorine into the melt at I4O-150° C.  Thiele, An”-, 1898, 303, p. 95 Anm.). It c stallizes in needles which melt at 190° (with decomposition), anidlis readily soluble in hot water. When heated strongly it is decomposed into ammonia and cyanuric acid. Baryta water hydrolyses it to carbon dioxide, ammonia and urea. With silver nitrate and caustic soda it yields a silver salt, Ag2C2H3N3O2. With nitric acid in the presence of sulphuric acid it yields a nitro derivative.

Thiourea, or sulphocarbamide, CS(NH2)2, is formed by prolonged fusion of ammonium thiocyanate (E. Reynolds, Ann., 1869, 150, p. 224), by passing sulphuretted hydrogen into an ethereal solution of cyan amide (E. Baumann, Bef., 1873, 6, p. 137 5), or by heating isopersulpho-cyanic acid (F. D. Chattaway, Jour. Chem. Soc., 1897, 71, p. 612). It crystallizes in thick prisms which melt at 180° C. and is readily soluble in water. When heated for some time with water to 140° C. in a sealed tube, it is transformed into ammonium thiocyanate, a similar result being obtained by heating the base alone for some hours to I6O"'I 7o° C. On heating alone for some hours to 170-180° C. it is converted into guanidine thiocyanate. It is hydrolysed by alkalis, giving carbon dioxide, ammonia and sulphuretted hydrogen. It is readily desulphurized by silver oxide, mercuric oxide or lead oxide. Potassium permanganate oxidizes it to urea (R. Maly, M onats., ISQO, II, p. 278). It acts as a weak base and forms salts with one equivalent of an acid. The alkyl derivatives of thiourea are obtained by the action of ammonia and of primary and secondary amines on the mustard oils (A. W. Hofmann, Ber., 1867, 1, p. 27):

CSNR-l-NH3=NH2-CS-NHR;CSNR+NH2R=R-NH-CS-NHR,

or by heating the amide salts of the alkyl dithio-carbaminic acids, viz., NR-CS-S(NH3R). The monoalkyl derivatives are desulphurized by lead hydroxide in the presence of sodium carbonate, the aB dialkyl and trialkyl derivatives being unaffected (A. E. Dixon, Jour. Chem. Soc., 1893, 63, p. 325). The dialkyl thioureas when digested with mercuric oxide and amines give guanidines. CS(NH'R)2-|-NHQR-l-HgO-9HgS-l-RN:C(NHR)2.

Thiourea and many o its unsymmetrical derivatives have marked physiological action; thiourea causes a slowing of the pulse and respiration, cardiac failure, and death in convulsions; phenylethyl- and acetyl-thiourea are actively toxic. The most important derivative pharmacologically is allyl-thiourea, also known as thiosinamine or rhodallin, NH2-CS-NH-CH2~CH:CH2. Thiosemicarbazfide, NH;-CS-NH-NI-12, prepared from hydrazine sulphate, potassium carbonate and thiocyanate (N. Freund, Bef., 1895, 28, p. 946; 1896, 29, p. 2501), crystallizes in long needles, which melt at I8H83° C. The addition of sodium nitrite to an aqueous solution of  hydrochloride converts it into amido-triaz-N:::

sulphol |. The hydrochloride with potassium cyanate I N

gives hydrazothio-carbon amide, ,NH2-CO-NH~NH-CS-NH2. Medicine.-Urea has been given in medicine in doses of 10 to 60 grs. either in mixture or hypodermic ally. It has been used with success as an anti periodic and anti pyre tic in ague, and also as a diuretic in gout and kidney affections. Thiosinamine is given internally in doses of é to I gr. in capsule. Larger doses usually upset the digestion. It has been used for the cure of lupus and of keloid, in which case it is administered hypodermic ally. In keloid 20 minims of a 10% solution is injected directly into the part. It causes a local reaction with absorption of the scar' tissue. For this reason it is used to remove corneal opacities, deafness due to thickening of the membrane, stricture of the oesophagus and hypertrophy of the pylorus, it has also been successful in the treatment of adhesive parametritis. Fibrolysin is a modified form of thiosinamine made by mixing it with sodium salicylate Fibrolysin is freely soluble and may be given in hypodermic or intra-muscular injection. Like thiosinamine it has a specific action on scar tissue and has been used in urethral strictures. Both these preparations should only be used in cases where it is possible to exclude any tuberculous foci, or by their action in breaking down protective fibrous tissues they may cause a quiescent lesion to become active. In large doses toxic symptoms are produced, death following on coma.

URETHANE, NH2CO2C2H5, the ethyl ester of carbamic acid, is synthesized from ammonia and chlorcarbonic ester or diethyl carbonate; by prolonged boiling of urea with alcohol (A. W. Hofmann, Ber., 1871, 4, p. 268); by the action of alcoholic hydrochloric acid on cyanogen; by the action of alcohol on urea chloride (L. Gattermann, Ann., 1888, 244, p. 40); and by warming alcoholic hydrochloric acid with an alcoholic solution of potassium cyanate (O. Folin, Amer. Chem. Jour., 1897, 19, p. 341). It crystallizes in large plates, readily soluble in water and melting at 49–50° C. When heated with ammonia to 180° C., it gives urea. Cold alcoholic potash decomposes it into potassium cyanate and alcohol.

Nitroso-urethane, NO·NH·CO2C2H5, formed by reducing ammonium nitro-urethane with zinc dust and glacial acetic acid (J. Thiele,